• 5-year DFS for favorable risk subset of NCI HR B-ALL (HR favorable) when treated with mBFM chemotherapy with a single high-dose methotrexate (HD MTX) Interim Maintenance (IM) phase and treatment duration of 2 years from the start of IM regardless of sex [ Time Frame: From EOC to first event (relapse, second malignant neoplasm, remission death) or date of last contact, assessed up to 5 years ]
  Will be estimated using the Kaplan-Meier method and standard errors and confidence intervals estimated by the method of Peto. Estimation of treatment effect will be done using ITT analysis based on randomized group.
• Incidence of adverse events for the integration of inotuzumab ozogamicin into the mBFM chemotherapy backbone in HR B-ALL [ Time Frame: Up to 5 years ]
  Graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Will be monitored and reported.
• 5-year event-free survival (EFS) for patients with mixed phenotype acute leukemia (MPAL) receiving mBFM HR B-ALL therapy that includes a second IM phase with Capizzi escalating intravenous MTX without leucovorin rescue plus pegaspargase (C-MTX) [ Time Frame: From study entry to first event (induction failure, Induction death, end of induction (EOI) minimal residual disease (MRD) >= 5%, EOC MRD >= 0.01%, relapse, second malignancy, remission death) or date of last contact, assessed up to 5 years ]
  Will be estimated using the Kaplan-Meier method and standard errors and confidence intervals estimated by the method of Peto. Estimation of treatment effect will be done using ITT analysis based on randomized group.
• 5-year EFS for patients with disseminated (Murphy stage III-IV) B-cell lymphoblastic lymphoma (B-LLy) receiving mBFM HR B-ALL therapy that includes a second IM phase with C-MTX [ Time Frame: From study entry to first event (progressive disease, induction death, relapse, second malignancy, remission death) or date of last contact, assessed up to 5 years ]
  Will be estimated using the Kaplan-Meier method and standard errors and confidence intervals estimated by the method of Peto. Estimation of treatment effect will be done using ITT analysis based on randomized group.

• 5-year DFS in National Cancer Institute (NCI) HR B-ALL (HR favorable [Fav]) when treated with mBFM chemotherapy with a single high-dose methotrexate (HD MTX) Interim Maintenance (IM) phase [ Time Frame: From EOC to first event (relapse, second malignant neoplasm, remission death) or date of last contact, assessed up to 5 years ]
  Will be estimated using the Kaplan-Meier method and standard errors and confidence intervals estimated by the method of Peto. Estimation of treatment effect will be done using ITT analysis based on randomized group.
• Incidence of adverse events for the integration of inotuzumab ozogamicin into the mBFM chemotherapy backbone in HR B-ALL [ Time Frame: Up to 5 years ]
  Graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Will be monitored and reported.
• 5-year event-free survival (EFS) for patients with mixed phenotype acute leukemia (MPAL) receiving mBFM HR B-ALL therapy that includes a second interim maintenance (IM) phase [ Time Frame: From study entry to first event (induction failure, Induction death, end of induction (EOI) minimal residual disease (MRD) >= 5%, EOC MRD >= 0.01%, relapse, second malignancy, remission death) or date of last contact, assessed up to 5 years ]
  Will be estimated using the Kaplan-Meier method and standard errors and confidence intervals estimated by the method of Peto. Estimation of treatment effect will be done using ITT analysis based on randomized group.
• 5-year EFS for patients with disseminated (Murphy stage III-IV) B-cell lymphoblastic lymphoma (B-LLy) receiving mBFM HR B-ALL therapy that includes a second IM phase [ Time Frame: From study entry to first event (progressive disease, induction death, relapse, second malignancy, remission death) or date of last contact, assessed up to 5 years ]
  Will be estimated using the Kaplan-Meier method and standard errors and confidence intervals estimated by the method of Peto. Estimation of treatment effect will be done using ITT analysis based on randomized group.

• Therapy administered to patients with MPAL who come off protocol therapy due to poor disease response to ALL therapy [ Time Frame: Up to 5 years ]
  Will be described.
• Disease response in patients with MPAL who come off protocol therapy due to poor disease response to ALL therapy [ Time Frame: Up to 5 years ]
  Will be described.
• Survival outcomes of patients with MPAL who come off protocol therapy due to poor disease response to ALL therapy [ Time Frame: Up to 5 years ]
  Will be described.
• Prevalence and significance of minimal marrow disease (MMD) at diagnosis and bone marrow MRD in disseminated B-LLy [ Time Frame: Up to 5 years ]
  Percentages with MMD at induction and MRD positivity at end of Induction will be described.
• Impact of four proposed interventions of varying intensities to enhance adherence to oral 6 mercaptopurine, with a randomization based upon baseline adherence measured during the first cycle of maintenance therapy [ Time Frame: Up to 5 years ]
  The main analyses will use mixed models including random effects to account for the multiple sites and longitudinal observations within patients. Will examine unadjusted associations of the primary outcome (MEMS-based adherence rate) with demographic, clinical and sociodemographic variables for the entire cohort (across 3 intervention arms). Those patient-level factors associated with the outcome will be included in the main model as fixed effects to improve the precision of the estimates. The basic model for adherence will include time and mean adherence during the baseline pre-intervention period and treatment group. It will also include interactions between time and both baseline adherence and intervention group to allow for intervention-specific trends and normal changes in adherence over time.

• Therapy administered to patients with MPAL who come off protocol therapy due to poor disease response to ALL therapy [ Time Frame: Up to 5 years ]
  Will be described.
• Disease response in patients with MPAL who come off protocol therapy due to poor disease response to ALL therapy [ Time Frame: Up to 5 years ]
  Will be described.
• Survival outcomes of patients with MPAL who come off protocol therapy due to poor disease response to ALL therapy [ Time Frame: Up to 5 years ]
  Will be described.
• Prevalence and significance of minimal marrow disease (MMD) at diagnosis and bone marrow MRD in disseminated B-LLy [ Time Frame: Up to 5 years ]
  Percentages with MMD at induction and MRD positivity at end of Induction will be described.
• Impact of proposed adherence-enhancing interventions, IP (intervention package as used in ACCL1033) versus (vs.) iIP (intensified intervention package) vs. pIP (patient/parent-established intervention package), on adherence to oral 6 mercaptopurine [ Time Frame: Up to 5 years ]
  The main analyses will use mixed models including random effects to account for the multiple sites and longitudinal observations within patients. Will examine unadjusted associations of the primary outcome (MEMS-based adherence rate) with demographic, clinical and sociodemographic variables for the entire cohort (across 3 intervention arms). Those patient-level factors associated with the outcome will be included in the main model as fixed effects to improve the precision of the estimates. The basic model for adherence will include time and mean adherence during the baseline pre-intervention period and treatment group. It will also include interactions between time and both baseline adherence and intervention group to allow for intervention-specific trends and normal changes in adherence over time.

This phase III trial studies whether inotuzumab ozogamicin added to post-induction chemotherapy for patients with High-Risk B-cell Acute Lymphoblastic Leukemia (B-ALL) improves outcomes. This trial also studies the outcomes of patients with mixed phenotype acute leukemia (MPAL), and B-lymphoblastic lymphoma (B-LLy) when treated with ALL therapy without inotuzumab ozogamicin. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a type of chemotherapy called calicheamicin. Inotuzumab attaches to cancer cells in a targeted way and delivers calicheamicin to kill them. Other drugs used in the chemotherapy regimen, such as cyclophosphamide, cytarabine, dexamethasone, doxorubicin, daunorubicin, methotrexate, leucovorin, mercaptopurine, prednisone, thioguanine, vincristine, and pegaspargase work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial will also study the outcomes of patients with mixed phenotype acute leukemia (MPAL) and disseminated B lymphoblastic lymphoma (B-LLy) when treated with high-risk ALL chemotherapy.

The overall goal of this study is to understand if adding inotuzumab ozogamicin to standard of care chemotherapy maintains or improves outcomes in High Risk B-cell Acute Lymphoblastic Leukemia (HR B-ALL). The first part of the study includes the first two phases of therapy: Induction and Consolidation. This part will collect information on the leukemia, as well as the effects of the initial treatment, in order to classify patients into post-consolidation treatment groups. On the second part of this study, patients will receive the remainder of the chemotherapy cycles (interim maintenance I, delayed intensification, interim maintenance II, maintenance), with some patients randomized to receive inotuzumab. Other aims of this study include investigating whether treating both males and females with the same duration of chemotherapy maintains outcomes for males who have previously been treated for an additional year compared to girls, as well as to evaluate the best ways to help patients adhere to oral chemotherapy regimens. Finally, this study will be the first to track the outcomes of subjects with disseminated B-cell Lymphoblastic Leukemia (B LLy) or Mixed Phenotype Acute Leukemia (MPAL) when treated with B-ALL chemotherapy.

PRIMARY OBJECTIVE:

I. To determine in a randomized manner if the addition of 2 blocks of inotuzumab ozogamicin to modified Berlin-Frankfurt-Munster (mBFM) chemotherapy will improve 5-year disease-free survival (DFS) in children and young adults with high-risk B-cell acute lymphoblastic leukemia (HR B-ALL).

SECONDARY OBJECTIVES:

I. To describe the 5-year DFS for a favorable risk subset of National Cancer Institute (NCI) HR B-ALL (HR-Fav) when treated with mBFM chemotherapy with a single high-dose methotrexate (HD-MTX) interim maintenance (IM) phase and treatment duration of 2 years from the start of IM regardless of sex.

II. To determine the toxicity and tolerability of inotuzumab ozogamicin integrated into the mBFM chemotherapy backbone in HR B-ALL.

III. To describe the 5-year event-free survival (EFS) for patients with mixed phenotype acute leukemia (MPAL) receiving mBFM HR B-ALL therapy that includes a second IM phase with Capizzi intravenous (IV) methotrexate (MTX) without leucovorin rescue plus pegaspargase (C-MTX).

IV. To describe the 5-year EFS for patients with disseminated (Murphy stage III-IV) B-cell lymphoblastic lymphoma (B-LLy) receiving mBFM HR B-ALL therapy that includes a second IM phase with C-MTX.

EXPLORATORY OBJECTIVES:

I. To describe the therapy administered, disease response, and survival outcomes of patients with MPAL who come off protocol therapy due to poor disease response to ALL therapy either during Induction, at end of induction (EOI), or at end of consolidation (EOC).

II. To define the prevalence and significance of minimal marrow disease (MMD) at diagnosis and bone marrow minimal residual disease (MRD) at EOI in disseminated B-LLy.

III. To determine the impact of proposed adherence-enhancing interventions on adherence to oral 6-mercaptopurine in patients with ALL.

OUTLINE: All patients receive the same Induction and Consolidation chemotherapy. Patients with HR-Fav B-ALL are assigned to Arm I. Patients with HR B-ALL are randomized to Arm II or III. Patients with MPAL are assigned to Arm IV, and patients with B-LLy are assigned to Arm V.

All patients with B-ALL receive Induction and Consolidation therapy:

INDUCTION: Patients receive cytarabine intrathecally (IT) on day 1 and central nervous system (CNS)2 patients also receive cytarabine IT on days 4, 5 or 6 and 11 or 12. Patients also receive vincristine intravenously (IV) or IV push over 1 minute on days 1, 8, 15, and 22, daunorubicin IV over 1-15 minutes days 1, 8, 15, and 22, pegaspargase intramuscularly (IM) or IV over 1-2 hours on day 4, and methotrexate IT on days 8 and 29 (and on days 15 and 22 for CNS3 patients). Patients < 10 years old receive dexamethasone orally (PO) twice daily (BID) or IV on days 1-14; patients >= 10 years old receive prednis(ol)one PO BID or IV on days 1-28. Treatment continues for 5 weeks in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29, cytarabine IV over 1-30 minutes or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine PO once daily (QD) on days 1-14 and 29-42, and methotrexate IT on days 1, 8, 15, and 22 (CNS3 patients receive methotrexate IT on days 1 and 8). Patients also receive vincristine IV or IV push over 1 minute on days 15, 22, 43, and 50, and pegaspargase IV over 1-2 hours or IM on days 15 and 43. Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity. Additionally, patients with testicular disease at diagnosis that does not resolve by the end of induction will undergo radiation therapy over 12 once daily fractions.

POST-CONSOLIDATION THERAPY: After Consolidation, based on clinical features and response, patients with B-ALL are designated as HR-Fav or HR B-ALL. Patients with HR-Fav B-ALL are assigned to Arm I. Patients with HR B-ALL are randomized to Arm II or III. Patients with MPAL and B-LLy are assigned to therapy arms (Arms IV and V) that are identical to Arm II. Patients that are < 10 years, have CNS1, no testicular leukemia, with favorable cytogenetics (ETV6 RUNX1 fusion or double trisomies [4 and 10]), =< 24 hours of steroids in the two weeks prior to diagnosis, and EOI MRD < 0.01% are assigned to Arm I. Patients with HR B-ALL who are surface CD22 positive at diagnosis and have MRD < 0.01% by the end of Consolidation, are randomized to either Arm II or III.

ARM I: HR-FAV B-ALL (Patients that are < 10 years, have CNS1 status, no testicular leukemia, with favorable cytogenetics (ETV6 RUNX1 fusion or double trisomies [4 and 10]), =< 24 hours of steroids in the two weeks prior to diagnosis, and EOI MRD < 0.01%)

INTERIM MAINTENANCE: Patients receive vincristine IV or IV push over 1 minute on days 1, 15, 29, and 43, high dose methotrexate IV over 24 hours on days 1, 15, 29, and 43, leucovorin PO or IV on days 3-4, 17-18, 31-32, and 45-46, mercaptopurine PO QD on days 1-14, 15-28, 29-42, and 43-56, and methotrexate IT on days 1 and 29. Treatment continues for 9 weeks in the absence of disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION (PART I): Patients receive methotrexate IT on day 1, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine IV or IV push over 1 minute on days 1, 8, and 15, doxorubicin IV over 1-15 minutes or up to 1 hour on days 1, 8, and 15, and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 4. Treatment (Parts I and II of Delayed Intensification) continues for 8 weeks in the absence of disease progression or unacceptable toxicity. Calaspargase pegol can only be given to patients less than 21 years of age.

DELAYED INTENSIFICATION (PART II): Patients receive cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42, cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39, methotrexate IT on days 29 and 36, vincristine IV or IV push over 1 minute on days 43 and 50, and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 43. Treatment (Parts I and II of Delayed Intensification) continues for 8 weeks in the absence of disease progression or unacceptable toxicity. Calaspargase pegol can only be given to patients less than 21 years of age.

MAINTENANCE: Patients receive methotrexate IT on days 1 and 29 for cycles 1-4, and day 1 for subsequent cycles. Patients also receive vincristine IV or IV push over 1 minute on day 1, prednisolone PO BID or IV on days 1-5, mercaptopurine PO QD on days 1-84, and methotrexate PO on days 8, 15, 22, (29 excluded in cycles 1-4), 36, 43, 50, 57, 64, 71, and 78. Cycles repeat every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.

Patients with HR B-ALL who have MRD < 0.01% by the end of Consolidation, and leukemic blasts positive for surface CD22 at diagnosis are randomized to Arm II or Arm III.

ARM II: HR B-ALL (CONTROL) INTERIM MAINTENANCE I: Patients receive vincristine IV or IV push over 1 minute on days 1, 15, 29 and 43, high dose methotrexate IV over 24 hours on days 1, 15, 29 and 43, leucovorin PO or IV on days 3-4, 17-18, 31-32, 45-46, mercaptopurine PO QD on days 1-14, 15-28, 29-42, and 43-56, and methotrexate IT on days 1 and 29. Treatment continues for 9 weeks in the absence of disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION (PART I): Patients receive methotrexate IT on day 1, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine IV or IV push over 1 minute on days 1, 8, and 15, doxorubicin IV over 1-15 minutes or up to 1 hour on days 1, 8, and 15, and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 4. Treatment (Parts I and II of Delayed Intensification) continues for 8 weeks in the absence of disease progression or unacceptable toxicity. Calaspargase pegol can only be given to patients less than 21 years of age.

DELAYED INTENSIFICATION (PART II): Patients receive cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42, cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39, methotrexate IT on days 29 and 36, vincristine IV or IV push over 1 minute on days 43 and 50, and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 43. Treatment (Parts I and II of Delayed Intensification) continues for 8 weeks in the absence of disease progression or unacceptable toxicity. Calaspargase pegol can only be given to patients less than 21 years of age.

INTERIM MAINTENANCE II: Patients receive vincristine IV or IV push over 1 minute on days 1, 11, 21, 31 and 41, methotrexate IV over 2-15 minutes or 10-15 minutes on days 1, 11, 21, 31, and 41, methotrexate IT on days 1 and 31, and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on days 2 and 22. Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity. Calaspargase pegol can only be given to patients less than 21 years of age.

ARM III: HR B-ALL (EXPERIMENTAL) INOTUZUMAB OZOGAMICIN (InO) BLOCK 1: Patients receive inotuzumab ozogamicin IV over 60 minutes on days 1, 8, and 15 and methotrexate IT on day 1. Treatment continues for 4 weeks in the absence of disease progression or unacceptable toxicity.

INTERIM MAINTENANCE I: Patients receive vincristine IV or IV push over 1 minute on days 1, 15, 29 and 43, high dose methotrexate IV over 24 hours on days 1, 15, 29, and 43, leucovorin PO or IV on days 3-4, 17-18, 31-32, and 45-46, mercaptopurine PO on days 1-14, 15-28, 29-42, and 43-56, and methotrexate IT on days 1 and 29. Treatment continues for 9 weeks in the absence of disease progression or unacceptable toxicity.

InO BLOCK 2: Patients receive inotuzumab ozogamicin IV over 60 minutes on days 1, 8, and 15. Treatment continues for 4 weeks in the absence of disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION (PART I): Patients receive methotrexate IT on day 1, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine IV or IV push over 1 minute on days 1, 8, and 15, doxorubicin IV over 1-15 minutes or up to 1 hour on days 1, 8, and 15, and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 4. Treatment (Parts I and II of Delayed Intensification) continues for 8 weeks in the absence of disease progression or unacceptable toxicity. Calaspargase pegol can only be given to patients less than 21 years of age.

DELAYED INTENSIFICATION (PART II): Patients receive cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42, cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39, methotrexate IT on days 29 and 36, vincristine IV or IV push over 1 minute on days 43 and 50, and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 43. Treatment (Parts I and II of Delayed Intensification) continues for 8 weeks in the absence of disease progression or unacceptable toxicity. Calaspargase pegol can only be given to patients less than 21 years of age.

INTERIM MAINTENANCE II: Patients receive vincristine IV or IV push over 1 minute on days 1, 11, 21, 31, and 41, methotrexate IV on days 1, 11, 21, 31, and 41, methotrexate IT on days 1 and 31, and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on days 2 and 22. Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity. Calaspargase pegol can only be given to patients less than 21 years of age.

ARMS II AND III: HR B-ALL MAINTENANCE: Patients receive vincristine IV or IV push over 1 minute on day 1, prednisolone PO BID or IV on days 1-5, mercaptopurine PO on days 1-84, methotrexate PO on days 8, 15, 22, 29 (excluded in cycles 1 and 2), 36, 43, 50, 57, 64, 71 and 78, and methotrexate IT on days 1 (and 29 of cycles 1-2 for patients who do not receive cranial radiation). Cycles repeat every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients with CNS3 disease undergo cranial radiation therapy over 10 fractions during the first 4 weeks.

ARM IV: MPAL INDUCTION: Patients receive cytarabine IT on day 1 and CNS2 patients also receive cytarabine IT on days 4, 5 or 6 and 11 or 12. Patients also receive vincristine IV or IV push over 1 minute on days 1, 8, 15, and 22, daunorubicin IV over 1-15 minutes days 1, 8, 15, and 22, pegaspargase IM or IV over 1-2 hours on day 4, and methotrexate IT on days 8 and 29 (and on days 15 and 22 for CNS3 patients). Patients < 10 years old receive dexamethasone PO BID or IV on days 1-14; patients >= 10 years old receive prednisolone PO BID or IV on days 1-28. Treatment continues for 5 weeks in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29, cytarabine IV over 1-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine PO on days 1-14 and 29-42, methotrexate IT on days 1, 8, 15, and 22 (excluded on days 15 and 22 for CNS3 patients), vincristine IV or IV push over 1 minute on days 15, 22, 43, and 50, and pegaspargase IV over 1-2 hours or IM on days 15 and 43. Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity. Patients with testicular disease at diagnosis that does not resolve by the end of induction will and continued evidence of testicular disease at end of induction undergo testicular radiation over 12 once-daily fractions.

ARM V: B-LLY INDUCTION: Patients receive cytarabine IT on day 1 and CNS2 patients also receive cytarabine IT on days 4, 5 or 6 and 11 or 12. Patients also receive vincristine IV or IV push over 1 minute on days 1, 8, 15, and 22, daunorubicin IV over 1-15 minutes days 1, 8, 15, and 22, pegaspargase IM or IV over 1-2 hours on day 4, and methotrexate IT on days 8 and 29 (and on days 15 and 22 for CNS3 patients). Patients < 10 years old receive dexamethasone PO BID or IV on days 1-14; patients >= 10 years old receive prednisolone PO BID or IV on days 1-28. Treatment continues for 5 weeks in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29, cytarabine IV over 1-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine PO on days 1-14 and 29-42, methotrexate IT on days 1, 8, 15, and 22 (excluded on days 15 and 22 CNS3 patients), vincristine IV or IV push over 1 minute on days 15, 22, 43, and 50, and pegaspargase IV over 1-2 hours or IM on days 15 and 43. Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity. Patients with testicular disease at diagnosis that does not resolve by the end of induction will and continued evidence of testicular disease at end of induction undergo testicular radiation therapy over 12 once-daily fractions.

ARM IV AND V: MPAL AND B-LLY (Post-Consolidation Therapy) INTERIM MAINTENANCE I: Patients receive vincristine IV or IV push over 1 minute on days 1, 15, 29, and 43, high dose methotrexate IV over 24 hours on days 1, 15, 29, and 43, leucovorin PO or IV on days 3-4, 17-18, 31-32, and 45-46, methotrexate IT on days 1 and 29 and mercaptopurine PO QD on days 1-14, 15-28, 29-42, and 43-56. Treatment continues for 9 weeks in the absence of disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION (PART I): Patients receive methotrexate IT on day 1, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine IV or IV push over 1 minute on days 1, 8, and 15, doxorubicin IV over 1-15 minutes or up to 1 hour on days 1, 8, and 15, and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 4. Treatment (Parts I and II of Delayed Intensification) continues for 8 weeks in the absence of disease progression or unacceptable toxicity. Calaspargase pegol can only be given to patients less than 21 years of age.

DELAYED INTENSIFICATION (PART II): Patients receive cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42, cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39, methotrexate IT on days 29 and 36, vincristine IV or IV push over 1 minute on days 43 and 50, and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 43. Treatment (Parts I and II of Delayed Intensification) continues for 8 weeks in the absence of disease progression or unacceptable toxicity. Calaspargase pegol can only be given to patients less than 21 years of age.

INTERIM MAINTENANCE II: Patients receive vincristine IV or IV push over 1 minute on days 1, 11, 21, 31, and 41, methotrexate IV or infusion over 2-15 minutes or 10-15 minutes on days 1, 11, 21, 31, and 41, methotrexate IT on days 1 and 31, and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on days 2 and 22. Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity. Calaspargase pegol can only be given to patients less than 21 years of age.

MAINTENANCE: Patients receive vincristine IV or IV push over 1 minute on days 1, prednisolone PO BID or IV on days 1-5, mercaptopurine PO on days 1-84, methotrexate PO on days 8, 15, 22, 29 (excluded in cycles 1 and 2), 36, 43, 50, 57, 64, 71, and 78, and methotrexate IT on days 1 (and 29 of cycles 1-2 for patients who do not receive cranial radiation). Cycles repeat every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients with CNS3 disease at diagnosis undergo cranial radiation therapy for 10 fractions over 4 weeks.

After completion of study treatment, patients are followed up at 4 weeks, then every 3 months for 2 years, every 4-6 months for the third year, then every 6-12 months for years 4-5.

• B Acute Lymphoblastic Leukemia
• B Lymphoblastic Lymphoma
• Central Nervous System Leukemia
• Mixed Phenotype Acute Leukemia
• Testicular Leukemia

• Drug: Calaspargase Pegol-mknl
  Given IV
  Other Names:

  • Asparaginase (Escherichia coli Isoenzyme II), Conjugate with alpha-(((2,5-Dioxo-1-pyrrolidinyl)oxy)carbonyl)-omega-methoxypoly(oxy-1,2-ethanediyl)
  • Asparlas
  • Calaspargase Pegol
  • EZN-2285
  • SC-PEG E. Coli L-Asparaginase
  • Succinimidyl Carbonate Monomethoxypolyethylene Glycol E. coli L-Asparaginase
• Drug: Cyclophosphamide
  Given IV
  Other Names:

  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamide Monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
• Drug: Cytarabine
  Given IV, IT, or SC
  Other Names:

  • .beta.-Cytosine arabinoside
  • 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-.beta.-D-Arabinofuranosylcytosine
  • 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-Beta-D-arabinofuranosylcytosine
  • 1.beta.-D-Arabinofuranosylcytosine
  • 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
  • 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
  • Alexan
  • Ara-C
  • ARA-cell
  • Arabine
  • Arabinofuranosylcytosine
  • Arabinosylcytosine
  • Aracytidine
  • Aracytin
  • Aracytine
  • Beta-Cytosine Arabinoside
  • CHX-3311
  • Cytarabinum
  • Cytarbel
  • Cytosar
  • Cytosine Arabinoside
  • Cytosine-.beta.-arabinoside
  • Cytosine-beta-arabinoside
  • Erpalfa
  • Starasid
  • Tarabine PFS
  • U 19920
  • U-19920
  • Udicil
  • WR-28453
• Drug: Daunorubicin Hydrochloride
  Given IV
  Other Names:

  • Cerubidin
  • Cerubidine
  • Cloridrato de Daunorubicina
  • Daunoblastin
  • Daunoblastina
  • Daunoblastine
  • Daunomycin Hydrochloride
  • Daunomycin, hydrochloride
  • Daunorubicin.HCl
  • Daunorubicini Hydrochloridum
  • FI-6339
  • Ondena
  • RP-13057
  • Rubidomycin Hydrochloride
  • Rubilem
• Drug: Dexamethasone
  Given PO or IV
  Other Names:

  • Aacidexam
  • Adexone
  • Aknichthol Dexa
  • Alba-Dex
  • Alin
  • Alin Depot
  • Alin Oftalmico
  • Amplidermis
  • Anemul mono
  • Auricularum
  • Auxiloson
  • Baycadron
  • Baycuten
  • Baycuten N
  • Cortidexason
  • Cortisumman
  • Decacort
  • Decadrol
  • Decadron
  • Decadron DP
  • Decalix
  • Decameth
  • Decasone R.p.
  • Dectancyl
  • Dekacort
  • Deltafluorene
  • Deronil
  • Desamethasone
  • Desameton
  • Dexa-Mamallet
  • Dexa-Rhinosan
  • Dexa-Scheroson
  • Dexa-sine
  • Dexacortal
  • Dexacortin
  • Dexafarma
  • Dexafluorene
  • Dexalocal
  • Dexamecortin
  • Dexameth
  • Dexamethasone Intensol
  • Dexamethasonum
  • Dexamonozon
  • Dexapos
  • Dexinoral
  • Dexone
  • Dinormon
  • Dxevo
  • Fluorodelta
  • Fortecortin
  • Gammacorten
  • Hemady
  • Hexadecadrol
  • Hexadrol
  • Lokalison-F
  • Loverine
  • Methylfluorprednisolone
  • Millicorten
  • Mymethasone
  • Orgadrone
  • Spersadex
  • TaperDex
  • Visumetazone
  • ZoDex
• Drug: Doxorubicin Hydrochloride
  Given IV
  Other Names:

  • 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI)
  • ADM
  • Adriacin
  • Adriamycin
  • Adriamycin Hydrochloride
  • Adriamycin PFS
  • Adriamycin RDF
  • ADRIAMYCIN, HYDROCHLORIDE
  • Adriamycine
  • Adriblastina
  • Adriblastine
  • Adrimedac
  • Chloridrato de Doxorrubicina
  • DOX
  • DOXO-CELL
  • Doxolem
  • Doxorubicin HCl
  • Doxorubicin.HCl
  • Doxorubin
  • Farmiblastina
  • FI 106
  • FI-106
  • hydroxydaunorubicin
  • Rubex
• Biological: Inotuzumab Ozogamicin
  Given IV
  Other Names:

  • Besponsa
  • CMC-544
  • Way 207294
  • WAY-207294
• Drug: Leucovorin Calcium
  Given PO or IV
  Other Names:

  • Adinepar
  • Calcifolin
  • Calcium (6S)-Folinate
  • Calcium Folinate
  • Calcium Leucovorin
  • Calfolex
  • Calinat
  • Cehafolin
  • Citofolin
  • Citrec
  • Citrovorum Factor
  • Cromatonbic Folinico
  • Dalisol
  • Disintox
  • Divical
  • Ecofol
  • Emovis
  • Factor, Citrovorum
  • Flynoken A
  • Folaren
  • Folaxin
  • FOLI-cell
  • Foliben
  • Folidan
  • Folidar
  • Folinac
  • Folinate Calcium
  • folinic acid
  • Folinic Acid Calcium Salt Pentahydrate
  • Folinoral
  • Folinvit
  • Foliplus
  • Folix
  • Imo
  • Lederfolat
  • Lederfolin
  • Leucosar
  • leucovorin
  • Rescufolin
  • Rescuvolin
  • Tonofolin
  • Wellcovorin
• Drug: Mercaptopurine
  Given PO
  Other Names:

  • 3H-Purine-6-thiol
  • 6 MP
  • 6 Thiohypoxanthine
  • 6 Thiopurine
  • 6-Mercaptopurine
  • 6-Mercaptopurine Monohydrate
  • 6-MP
  • 6-Purinethiol
  • 6-Thiopurine
  • 6-Thioxopurine
  • 6H-Purine-6-thione, 1,7-dihydro- (9CI)
  • 7-Mercapto-1,3,4,6-tetrazaindene
  • Alti-Mercaptopurine
  • Azathiopurine
  • Bw 57-323H
  • Flocofil
  • Ismipur
  • Leukerin
  • Leupurin
  • Mercaleukim
  • Mercaleukin
  • Mercaptina
  • Mercaptopurinum
  • Mercapurin
  • Mern
  • NCI-C04886
  • Puri-Nethol
  • Purimethol
  • Purine, 6-mercapto-
  • Purine-6-thiol (8CI)
  • Purine-6-thiol, monohydrate
  • Purinethiol
  • Purinethol
  • U-4748
  • WR-2785
• Drug: Methotrexate
  Given IT or IV
  Other Names:

  • Abitrexate
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate
  • Mexate-AQ
  • MTX
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039
• Drug: Pegaspargase
  Given IV or IM
  Other Names:

  • L-Asparaginase with Polyethylene Glycol
  • Oncaspar
  • Oncaspar-IV
  • PEG-Asparaginase
  • PEG-L-Asparaginase
  • PEG-L-Asparaginase (Enzon - Kyowa Hakko)
  • PEGLA
  • Polyethylene Glycol L-Asparaginase
  • Polyethylene Glycol-L-Asparaginase
• Drug: Prednisolone
  Given PO or IV
  Other Names:

  • (11beta)-11,17,21-Trihydroxypregna-1,4-diene-3,20-dione
  • .delta.1-Hydrocortisone
  • Adnisolone
  • Aprednislon
  • Capsoid
  • Cortalone
  • Cortisolone
  • Dacortin H
  • Decaprednil
  • Decortin H
  • Delta(1)Hydrocortisone
  • Delta- Cortef
  • Delta-Cortef
  • Delta-Diona
  • Delta-F
  • Delta-Phoricol
  • Delta1-dehydro-hydrocortisone
  • Deltacortril
  • Deltahydrocortisone
  • Deltasolone
  • Deltidrosol
  • Dhasolone
  • Di-Adreson-F
  • Dontisolon D
  • Estilsona
  • Fisopred
  • Frisolona
  • Gupisone
  • Hostacortin H
  • Hydeltra
  • Hydeltrasol
  • Klismacort
  • Kuhlprednon
  • Lenisolone
  • Lepi-Cortinolo
  • Linola-H N
  • Linola-H-Fett N
  • Longiprednil
  • Metacortandralone
  • Meti Derm
  • Meticortelone
  • Opredsone
  • Panafcortelone
  • Precortisyl
  • Pred-Clysma
  • Predeltilone
  • Predni-Coelin
  • Predni-Helvacort
  • Prednicortelone
  • Prednisolonum
  • Prelone
  • Prenilone
  • Sterane
• Other: Questionnaire Administration
  Ancillary studies
• Radiation: Radiation Therapy
  Undergo testicular radiation therapy
  Other Names:

  • Cancer Radiotherapy
  • ENERGY_TYPE
  • Irradiate
  • Irradiated
  • Irradiation
  • Radiation
  • Radiation Therapy, NOS
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
• Radiation: Radiation Therapy
  Undergo cranial radiation therapy
  Other Names:

  • Cancer Radiotherapy
  • ENERGY_TYPE
  • Irradiate
  • Irradiated
  • Irradiation
  • Radiation
  • Radiation Therapy, NOS
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
• Drug: Thioguanine
  Given PO
  Other Names:

  • 2-Amino 6MP
  • 2-Amino-1,7-dihydro-6H-purine-6-thione
  • 2-Amino-6-mercaptopurine
  • 2-Amino-6-purinethiol
  • 2-Aminopurin-6-thiol
  • 2-Aminopurine-6(1H)-thione
  • 2-Aminopurine-6-thiol
  • 2-Aminopurine-6-thiol Hemihydrate
  • 2-Mercapto-6-aminopurine
  • 6-Amino-2-mercaptopurine
  • 6-Mercapto-2-aminopurine
  • 6-Mercaptoguanine
  • 6-TG
  • 6H-Purine-6-thione, 2-amino-1,7-dihydro- (9CI)
  • BW 5071
  • Lanvis
  • Tabloid
  • Thioguanine Hemihydrate
  • Thioguanine Hydrate
  • Tioguanin
  • Tioguanine
  • Wellcome U3B
  • WR-1141
  • X 27
• Drug: Vincristine Sulfate
  Given IV or IV push
  Other Names:

  • Kyocristine
  • Leurocristine Sulfate
  • Leurocristine, sulfate
  • Oncovin
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate

• Experimental: Arm I (HR-FAV B-ALL)
  See detailed description for Arm I
  Interventions:

  • Drug: Calaspargase Pegol-mknl
  • Drug: Cyclophosphamide
  • Drug: Cytarabine
  • Drug: Daunorubicin Hydrochloride
  • Drug: Dexamethasone
  • Drug: Doxorubicin Hydrochloride
  • Drug: Leucovorin Calcium
  • Drug: Mercaptopurine
  • Drug: Methotrexate
  • Drug: Pegaspargase
  • Drug: Prednisolone
  • Other: Questionnaire Administration
  • Drug: Thioguanine
  • Drug: Vincristine Sulfate
• Active Comparator: Arm II (HR B-ALL CONTROL)
  See detailed description for Arm II.
  Interventions:

  • Drug: Calaspargase Pegol-mknl
  • Drug: Cyclophosphamide
  • Drug: Cytarabine
  • Drug: Daunorubicin Hydrochloride
  • Drug: Dexamethasone
  • Drug: Doxorubicin Hydrochloride
  • Drug: Leucovorin Calcium
  • Drug: Mercaptopurine
  • Drug: Methotrexate
  • Drug: Pegaspargase
  • Drug: Prednisolone
  • Other: Questionnaire Administration
  • Radiation: Radiation Therapy
  • Drug: Thioguanine
  • Drug: Vincristine Sulfate
• Experimental: Arm III (HR B-ALL EXPERIMENTAL)
  See detailed description for Arm III.
  Interventions:

  • Drug: Calaspargase Pegol-mknl
  • Drug: Cyclophosphamide
  • Drug: Cytarabine
  • Drug: Daunorubicin Hydrochloride
  • Drug: Dexamethasone
  • Drug: Doxorubicin Hydrochloride
  • Biological: Inotuzumab Ozogamicin
  • Drug: Leucovorin Calcium
  • Drug: Mercaptopurine
  • Drug: Methotrexate
  • Drug: Pegaspargase
  • Other: Questionnaire Administration
  • Radiation: Radiation Therapy
  • Drug: Thioguanine
  • Drug: Vincristine Sulfate
• Experimental: Arm IV (MPAL)
  See detailed description for Arm IV.
  Interventions:

  • Drug: Calaspargase Pegol-mknl
  • Drug: Cyclophosphamide
  • Drug: Cytarabine
  • Drug: Daunorubicin Hydrochloride
  • Drug: Dexamethasone
  • Drug: Doxorubicin Hydrochloride
  • Drug: Leucovorin Calcium
  • Drug: Mercaptopurine
  • Drug: Methotrexate
  • Drug: Pegaspargase
  • Drug: Prednisolone
  • Other: Questionnaire Administration
  • Radiation: Radiation Therapy
  • Radiation: Radiation Therapy
  • Drug: Thioguanine
  • Drug: Vincristine Sulfate
• Experimental: ARM V (B-LLY)
  See detailed description for Arm V.
  Interventions:

  • Drug: Calaspargase Pegol-mknl
  • Drug: Cyclophosphamide
  • Drug: Cytarabine
  • Drug: Daunorubicin Hydrochloride
  • Drug: Dexamethasone
  • Drug: Doxorubicin Hydrochloride
  • Drug: Leucovorin Calcium
  • Drug: Methotrexate
  • Drug: Pegaspargase
  • Drug: Prednisolone
  • Other: Questionnaire Administration
  • Radiation: Radiation Therapy
  • Radiation: Radiation Therapy
  • Drug: Thioguanine
  • Drug: Vincristine Sulfate

Inclusion Criteria:

• B-ALL and MPAL patients must be enrolled on APEC14B1 and consented to eligibility studies (Part A) prior to treatment and enrollment on AALL1732. Note that central confirmation of MPAL diagnosis must occur within 7 business days after enrollment for MPAL patients. If not performed within this time frame, patients will be taken off protocol.
• APEC14B1 is not a requirement for B-LLy patients but for institutional compliance every patient should be offered participation in APEC14B1. B-LLy patients may directly enroll on AALL1732.

• White blood cell count (WBC) criteria for patients with B-ALL (within 7 days prior to the start of protocol-directed systemic therapy):

  • Age 1-9.99 years: WBC >= 50,000/uL
  • Age 10-24.99 years: Any WBC

  • Age 1-9.99 years: WBC < 50,000/uL with:

    • Testicular leukemia
    • CNS leukemia (CNS3)
    • Steroid pretreatment.

• White blood cell count (WBC) criteria for patients with MPAL (within 7 days prior to the start of protocol-directed systemic therapy):

  • Age 1-24.99 years: any WBC.

• Patient has newly diagnosed B-ALL or MPAL (by World Health Organization [WHO] 2016 criteria) with > 25% blasts on a bone marrow (BM) aspirate;

  • OR If a BM aspirate is not obtained or is not diagnostic of acute leukemia, the diagnosis can be established by a pathologic diagnosis of acute leukemia on a BM biopsy;
  • OR A complete blood count (CBC) documenting the presence of at least 1,000/uL circulating leukemic cells if a bone marrow aspirate or biopsy cannot be performed.
• Patient has newly diagnosed B-LLy Murphy stages III or IV.
• Patient has newly diagnosed B-LLy Murphy stages I or II with steroid pretreatment.
• Note: For B-LLy patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to B-ALL. For tissue processed by other means (i.e., paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of B-LLy defined by the submitting institution will be accepted.
• All patients and/or their parents or legal guardians must sign a written informed consent.
• All institutional, Food and Drug Administration (FDA), and NCI requirements for human studies must be met.

Exclusion Criteria:

• Patients with Down syndrome are not eligible (patients with Down syndrome and B-ALL are eligible for AALL1731, regardless of NCI risk group).
• With the exception of steroid pretreatment or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for the current diagnosis of B-ALL, MPAL, or B-LLy

  相关推荐

  美国治疗医生

  治疗医院

  • 
    梅奥诊所

    美国最佳医院荣誉榜第1名
  • 
    克利夫兰诊所

    美国最佳医院荣誉榜第2名
  • 
    约翰霍普金斯医院

    美国最佳医院荣誉榜第3名
  • 
    麻省总医院

    美国最佳医院荣誉榜第4名
  • 
    密歇根大学医院

    美国最佳医院荣誉榜第5名
  • 
    倉敷中央医院

    日本综合排名第1名
  • 
    順天堂医院

    日本综合排名第2名
  • 
    藤田医科大学医院（原藤田保健大学医院)

    日本综合排名第3名
  • 
    北里大学医院

    日本综合排名第4名
  • 
    東京医科大学医院

    日本综合排名第5名

  新药特效药

  • 阿克拉比星
  • 依托泊苷
  • 表柔比星
  • 环磷酰胺
  • 环磷酰胺
  • 环磷酰胺
  • 吡拉比星
  • 甲氨蝶呤
  • 甲氨蝶呤
  • 墨卡托布丁

  治疗案例

  • 希瑟·沃尔特斯-病人故事
  • 凯西头血癌的故事成人急性淋巴细胞白血病（全部）
  • 威廉·扬克（William Yank）血液癌故事，急性淋巴细胞白血病，B型细胞
  • Veronica Balanza白血病的故事急性淋巴细胞白血病，B细胞，PH-
  • 埃文·莱丝勒（Evan Lessler）血液癌故事讲述成人急性淋巴细胞白血病（ALL）
  • 克里斯汀·米尔斯（Christine Mills）白血病故事：急性淋巴细胞白血病，T细胞
  • 西亚拉·托特（Ciara Toth）血癌故事讲述急性淋巴细胞白血病
  • 萨沙塔诺里（Sasha Tanori）的血液癌故事说明了急性髓细胞性白血病（AML）
  • 莱斯利·泰瑟（Leslie Tysseling）的血癌故事讲述急性早幼粒细胞白血病（APL）
  • 路易莎·里昂（Luisa Lyons）血液癌症故事讲述急性髓性白血病，Flit 3突变

  前沿医讯

  • 表观遗传学：它如何运作以及对癌症研究意味着什么
  • FDA批准了针对淋巴瘤患者的第二种CAR T细胞疗法
  • 使用大胆策略增强CAR T细胞疗法
  • 什么是癌症？常见问题解答
  • 遗传在小儿白血病中起什么作用？
  • 是什么导致癌症？要了解的9个风险因素
  • 什么是中性粒细胞减少症，如何治疗？
  • 对于肿瘤学家和癌症患者，波士顿马拉松赛是个人的
  • 基因疗法如何用于治疗癌症？
  • CAR T细胞疗法患者的治疗方法